Arya M. Sharma, MD

Dr. med. Jens Ringel

Since my first publication in 1987, I have authored or co-authored well over 300 peer-reviewed papers, about half of which are on topics related to obesity. This year, I thought I would dedicate my Saturday posts to reviewing some of these papers and sharing the stories behind them. If nothing else, it may point readers to some of the topics that have found my interest me over the years.

The first of my obesity papers to come up in a PubMed search is that of my MD-doctoral student Jens Ringel, published in Biochem Biophys Res Commun (1999), looking at a common genetic variant of the peroxisome proliferator activated receptor-gamma (PPARg), a nuclear receptor, that regulates adipocyte differentiation and possibly lipid metabolism and insulin sensitivity.

In this study, we specifically examined the allelic frequencies of the missense C –> G mutation at codon 12 of this gene, which results in the substitution of proline with alanine (Pro12Ala) in subjects with type 1 (n = 522) and type 2 (n = 503) diabetes compared to that in healthy controls (n = 310) and found no differences between these groups. There was also no significant relationship between dyslipoproteinemia or obesity and the PPARg Pro12Ala genotype.

Thus, these findings did not support the hypothesis that this genetic variant is strongly associated with diabetes, obesity, or dyslipidemia in patients with type 1 or type 2 diabetes mellitus and we concluded that this genetic marker is therefore unlikely to serve as a clinically useful predictor of these disorders in Caucasian patients with diabetes mellitus.

In hindsight such an assumption may appear rather naive, given that today we know that it takes far larger sample sizes (10s of thousands of subjects) and far more sophisticated analyses to stand even a remote chance of identifying genes for complex diseases. But back in 1999, when this paper was published, many of us were churning out papers looking at single nucleotide polymorphisms (SNPs) of candidate genes in a few hundred samples.

According to Google Scholar, this paper has been cited 134 times, so I guess someone did find this study of interest after all.

AMS
Edmonton, Alberta

Ringel J, Engeli S, Distler A, & Sharma AM (1999). Pro12Ala missense mutation of the peroxisome proliferator activated receptor gamma and diabetes mellitus. Biochemical and biophysical research communications, 254 (2), 450-3 PMID: 9918859

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In my continuing coverage from the World Diabetes Congress, I thought it may be appropriate to share with my readers the Global Diabetes Plan 2011-2012, recently released by the International Diabetes Federation.

The objectives of this ambitious plan are to

1) Improve health outcomes of people with diabetes - early diagnosis, cost effective treatment and self-management education can prevent or significantly delay devastating diabetes-related complications and save lives.

2) Prevent the development of type 2 diabetes - lifestyle interventions and socially responsible policies and market interventions within and beyond the health sector can promote healthy nutrition and physical activity and prevent diabetes.

3) Stop discrimination against people with diabetes - people with diabetes can play an important role in their own health outcomes and combating diabetes more generally. Supportive legal and policy frameworks, awareness campaigns and patient-centred services uphold the rights of people with diabetes and prevent discrimination.

The key strategy of the plan is to call on governments to implement National Diabetes Programmes - Comprehensive policy and delivery approaches enhance the organisation, quality and reach of diabetes prevention and care. It is feasible and desirable for all countries to have a national diabetes programme and successful models are already in place in some countries.

The hope is that this strategy will deliver the following results:

1) Strengthen institutional frameworks - strengthen UN and country-level leadership across multiple sectors to ensure coherent, innovative and effective global and national responses to diabetes, and achieve the best possible return on investment.

2) Integrate and optimise human resources and health services - re-orient, equip and build capacity of health systems to respond effectively to the challenge of diabetes through training and workforce devel- opment, particularly at primary care level.

3) Review and streamline supply systems - optimise the provision of essential diabetes medicines and technologies through reliable and transparent procurement and distribution systems.

4) Generate and use research evidence strategically - develop a prioritised research agenda, build research capacity and apply evidence to policy and practice.

5) Monitor, evaluate and communicate outcomes - use health information systems and robust moni- toring and evaluation to assess progress.

6) Allocate appropriate and sustainable domestic and international resources - achieve innovative, sustained and predict- able resourcing for diabetes, including Official Development Assistance (ODA) for low-and middle-income countries.

7) Adopt a whole of society approach - engage governments, the private sector and civil society (including healthcare workers, academia and people with diabetes) in working together to turn the tide on diabetes.

With regard to point 7, the report comes out very much in favour of engaging business and industry in an attempt to encourage:

- property developers to improve building design for physical activity and social inclusion.

- the food industry to support wide availability of nutritious and affordable food and bever- ages, reduce marketing of unhealthy food and to adopt socially responsible business policies and practices.

In fact, this afternoon (too late for this blog post), I will attend a debate on how such interactions with industry could work and perhaps, more specifically, whether or not an organization like the IDF (or for that matter any NGO) should accept funding from industry - including those, who may be deemed to be “part of the problem”.

As the Scientific Director and CEO of the Canadian Obesity Network, Canada’s only national non-profit organization dedicated to obesity prevention and management, which, despite enthusiastic public proclamations by health ministers on their intent to address the obesity problem, currently has no sustainable public funding, this topic is obviously of considerable interest.

I look forward to reporting, on what I hope will be an enlightening debate in tomorrow’s post.

AMS
Dubai, UAE

p.s. a copy of the IDF Global Diabetes Plan is available here

As regular readers will recall, this week I am attending the World Diabetes Congress - with well over 14,000 attendees, the largest ever world congress on this issue.

For readers, who are not familiar with the International Diabetes Federation (!DF), it may be worth pointing out that the IDF is an umbrella organization of over 200 national diabetes associations in over 160 countries. IDF’s national diabetes associations are divided into the following regions: Africa (AFR),Europe (EUR),Middle East and North Africa (MENA), North America and Caribbean (NAC),South and Central America (SACA), South East Asia (SEA) and Western Pacific (WP).

Thus, the IDF, which has been in operation since 1950, represents the interests of the growing number of people with diabetes and those at risk.

The mission of IDF is to:

“advance diabetes care, prevention and a cure worldwide.”

Its strategic goals are to:

Drive change at all levels, from local to global, to prevent diabetes and increase access to essential medicines.

Develop and encourage best practice in diabetes policy, management and education.

Advance diabetes treatment, prevention and cure through scientific research.

Advance and protect the rights of people with diabetes, and combat discrimination.

(interestingly, these goals are reminiscent of those of the Canadian Obesity Network, Canada’s National Obesity organization, with the difference perhaps that obesity is a much larger issue than just diabetes).

Amongst the many activities and resources provided by the IDF, one that readers may find of particular interest (and one that can be a great time waster for readers who are looking for new ways to procrastinate) is the interactive World Diabetes Atlas, now in its 5th edition (just released last month).

The atlas exemplifies just how many folks around the work (especially in South Asia) are affected by type 2 diabetes - interesting, an obesity map of the world would look almost identical, except that the numbers would be far greater (only about 15-20% of obese people actually go on to develop diabetes - but may well have other weight-related health problems).

One of the notable features of this congress is the massive industry exhibit - not quite as extensive as those at cardiology or oncology meetings but, by a significant magnitude of scale, larger than any industry exhibits seen at obesity meetings. This is of course because diabetes management (although never curative) is big business, with countless new classes of anti-diabetic drugs in the pharma pipelines to add to the many oral and injectable treatments that are already out there (not to mention the vast blood glucose monitoring and insulin pump industries).

While there is no doubt that these companies are providing excellent products and services that make the life of people with diabetes so much easier and help reduce the horrible risks of this condition, one can only wish that in the not too distant future, a similar arsenal of treatments and management tools may become available for those struggling with obesity and its myriad sequelae (EOSS 2-4).

While the hope is not to ‘cure’ obesity (I am not sure we can actually do that), having effective obesity treatments that fill the vast therapeutic gap between ‘eat-less-move-more’ and bariatric surgery are urgently needed.

Not only would this reduce the global burden of diabetes but hopefully also the global burden of the over 20 other chronic conditions that are strongly associated with excess weight (including many cancers).

Unfortunately, neither the current regulatory framework for new launching new obesity medications nor the necessary investment into training health professionals to better manage obesity or into research to find better treatments comes close to the actual size of the problem (just count how many Canadian medical schools actually have a chair in obesity - I know of two).

So although there is an appreciable number of talks and sessions on obesity (including the ones the I am giving and chairing), the focus of this congress is of course on managing diabetes and its complications.

Unfortunately, as I have said before, managing type 2 diabetes without addressing obesity is largely ‘palliative’ care.

Obviously, not a popular view at this conference.

AMS,
Dubai, UAE

This week I am attending the World Congress on Obesity, organized by the International Diabetes Federation.

As one would imagine, the program here is chock-full of talks on obesity - everything from the impact of excess weight on insulin resistance and diabetes risk to basic science talks on energy and appetite regulation.

This morning I will be presenting a 60 min course on obesity management in diabetes and later this week, I will be co-chairing a session on bariatric surgery.

At this moment I am sitting in a session on obesity in ethnic populations listening to talks on why, for e.g., the very concept of weight loss goes against many traditional cultures and indeed, losing weight or being skinny is neither socially desirable nor a sign of good health.

This of course, proves a challenge as type 2 diabetes becomes more rampant in these populations (like India, South America, Australian Aboriginals, etc.) where there is little interest in weight management as an important principle in diabetes prevention and management.

I certainly look forward to a most interesting week here in Dubai and learning more about diabetes and its management from my colleagues around the world.

AMS
Dubai, UAE

Regular readers should by now be quite familiar with the accumulating data suggesting that your risk for future development of obesity, diabetes, and possibly other metabolic diseases, may begin in the womb.

This topic is nicely reviewed in a paper by Marie-Claude Battista and colleagues from the University of Sherbrooke, Quebec, published in Experimental Diabetes Research.

In this paper, the authors not only discuss the relationship between maternal obesity and pregnancy risk (for both mother and child) but also discuss the complex factors that link excess weight to gestational diabetes.

They then extensively review the animal data that shows how intra-uterine epigenetic modifications can lead to a (permanent) metabolic adaptation that substantially increases the risk for obesity and diabetes in the offspring.

Finally, they critically discuss the emerging human data demonstrating the impact of lifestyle and bariatric surgery on both maternal and fetal health and the ability of these interventions to possibly break the vicious circle that perpetuates the transmission of obesity and metabolic conditions to the next generations

As the authors conclude:

“Fetal programming of metabolic function induced by obesity and GDM may have intergenerational effect and thus, perpetuate the burden of such conditions. Mechanisms by which reprogramming of fetal function might occur is directly through maternal metabolic and hormonal effects, epigenetic alterations or impaired placental function. Periconceptional weight loss interventions have demonstrated their ability to reverse the impacts of maternal obesity and GDM on the child and are of great importance for the prevention of future cardiometabolic risks in the offspring, and may thus be the best approach to break the vicious circle of intergenerational propagation of obesity and diabetes.”

They, however also caution that:

“…the nature and the timing of intervention should be carefully considered because it could also by itself induce organ reprogramming and potential long-term effect on the offspring.”

Not an easy topic (and certainly not an easy read) given the complexity of the emerging molecular, metabolic and genetic animal and human data on this issue.

However, certainly a topic that cannot be ignored in any discussion about finding solutions to the obesity epidemic.

AMS
Leipzig, Germany

Battista MC, Hivert MF, Duval K, & Baillargeon JP (2011). Intergenerational cycle of obesity and diabetes: how can we reduce the burdens of these conditions on the health of future generations? Experimental diabetes research, 2011 PMID: 22110473